Globally, in 2013, 60,400 kilograms of cannabis were produced legally.[5] In 2013 between 128 and 232 million people are thought to have used cannabis (2.7% to 4.9% of the global population between the ages of 15 and 65).[6]

Description

Cannabis is an annual, dioecious, floweringherb. The leaves are palmately compound or digitate, with serrateleaflets.[7] The first pair of leaves usually have a single leaflet, the number gradually increasing up to a maximum of about thirteen leaflets per leaf (usually seven or nine), depending on variety and growing conditions. At the top of a flowering plant, this number again diminishes to a single leaflet per leaf. The lower leaf pairs usually occur in an opposite leaf arrangement and the upper leaf pairs in an alternate arrangement on the main stem of a mature plant.

The leaves have a peculiar and diagnostic venation pattern that enables persons poorly familiar with the plant to distinguish a Cannabis leaf from unrelated species that have confusingly similar leaves (see illustration). As is common in serrated leaves, each serration has a central vein extending to its tip. However, the serration vein originates from lower down the central vein of the leaflet, typically opposite to the position of, not the first notch down, but the next notch. This means that on its way from the midrib of the leaflet to the point of the serration, the vein serving the tip of the serration passes close by the intervening notch. Sometimes the vein will actually pass tangent to the notch, but often it will pass by at a small distance, and when that happens a spur vein (occasionally a pair of such spur veins) branches off and joins the leaf margin at the deepest point of the notch. This venation pattern varies slightly among varieties, but in general it enables one to tell Cannabis leaves from superficially similar leaves without difficulty and without special equipment. Tiny samples of Cannabis plants also can be identified with precision by microscopic examination of leaf cells and similar features, but that requires special expertise and equipment.[8]

The plant is believed to have originated in the mountainous regions northwest of the Himalayas.[citation needed] It is also known as hemp, although this term is often used to refer only to varieties of Cannabis cultivated for non-drug use.

Reproduction

Cannabis normally has imperfectflowers, with staminate "male" and pistillate "female" flowers occurring on separate plants.[9] It is not unusual, however, for individual plants to bear both male and female flowers.[10] Although monoecious plants are often referred to as "hermaphrodites," true hermaphrodites (which are less common) bear staminate and pistillate structures on individual flowers, whereas monoecious plants bear male and female flowers at different locations on the same plant. Male flowers are normally borne on loose panicles, and female flowers are borne on racemes.[11] "At a very early period the Chinese recognized the Cannabis plant as dioecious,"[12] and the (c. 3rd century BCE) Erya dictionary defined xi枲 "male Cannabis" and fu莩 (or ju苴) "female Cannabis".[13]

Biochemistry and drugs

Cannabis plants produce a group of chemicals called cannabinoids, which produce mental and physical effects when consumed.

Cannabinoids, terpenoids, and other compounds are secreted by glandular trichomes that occur most abundantly on the floral calyxes and bracts of female plants.[16] As a drug it usually comes in the form of dried flower buds (marijuana), resin (hashish), or various extracts collectively known as hashish oil.[4] In the early 20th century, it became illegal in most of the world to cultivate or possess Cannabis for sale or personal use.

Root system side view

Root system top view

Micrograph sativa (left), indica (right)

Chromosomes and genome

Cannabis, like many organisms, is diploid, having a chromosome complement of 2n=20, although polyploid individuals have been artificially produced.[17] The first genome sequence of Cannabis, which is estimated to be 820 Mb in size, was published in 2011 by a team of Canadian scientists.[18]

plants cultivated for fiber and seed production, described as low-intoxicant, non-drug, or fiber types.

plants cultivated for drug production, described as high-intoxicant or drug types.

escaped, hybridised, or wild forms of either of the above types.

Cannabis plants produce a unique family of terpeno-phenolic compounds called cannabinoids, which produce the "high" one experiences from consuming marijuana. There are 483 identifiable chemical constituents known to exist in the cannabis plant,[23] and at least 85 different cannabinoids have been isolated from the plant.[24] The two cannabinoids usually produced in greatest abundance are cannabidiol (CBD) and/or Δ9-tetrahydrocannabinol (THC), but only THC is psychoactive.[25] Since the early 1970s, Cannabis plants have been categorized by their chemical phenotype or "chemotype," based on the overall amount of THC produced, and on the ratio of THC to CBD.[26] Although overall cannabinoid production is influenced by environmental factors, the THC/CBD ratio is genetically determined and remains fixed throughout the life of a plant.[27] Non-drug plants produce relatively low levels of THC and high levels of CBD, while drug plants produce high levels of THC and low levels of CBD. When plants of these two chemotypes cross-pollinate, the plants in the first filial (F1) generation have an intermediate chemotype and produce similar amounts of CBD and THC. Female plants of this chemotype may produce enough THC to be utilized for drug production.[26][28]

Top of Cannabis plant in vegetative growth stage

Whether the drug and non-drug, cultivated and wild types of Cannabis constitute a single, highly variable species, or the genus is polytypic with more than one species, has been a subject of debate for well over two centuries. This is a contentious issue because there is no universally accepted definition of a species.[29] One widely applied criterion for species recognition is that species are "groups of actually or potentially interbreeding natural populations which are reproductively isolated from other such groups."[30] Populations that are physiologically capable of interbreeding, but morphologically or genetically divergent and isolated by geography or ecology, are sometimes considered to be separate species.[30]Physiological barriers to reproduction are not known to occur within Cannabis, and plants from widely divergent sources are interfertile.[17] However, physical barriers to gene exchange (such as the Himalayan mountain range) might have enabled Cannabis gene pools to diverge before the onset of human intervention, resulting in speciation.[31] It remains controversial whether sufficient morphological and genetic divergence occurs within the genus as a result of geographical or ecological isolation to justify recognition of more than one species.[32][33][34]

History of cannabis

Cannabis sativa appears naturally in many tropical and humid parts of the world. Its use as a mind-altering drug has been documented by archaeological finds in prehistoric societies in Euro-Asia and Africa.[35]

The oldest written record of cannabis usage is the Greek historian Herodotus's reference to the central Eurasian Scythians taking cannabis steam baths.[36] His (c. 440 BCE) Histories records, "The Scythians, as I said, take some of this hemp-seed [presumably, flowers], and, creeping under the felt coverings, throw it upon the red-hot stones; immediately it smokes, and gives out such a vapour as no Grecian vapour-bath can exceed; the Scyths, delighted, shout for joy."[37] Classical Greeks and Romans were using cannabis, while in the Middle East, use spread throughout the Islamic empire to North Africa. In 1545 cannabis spread to the western hemisphere where Spaniards imported it to Chile for its use as fiber. In North America cannabis, in the form of hemp, was grown for use in rope, clothing and paper.[38][39][40][41]

Early classifications

Relative size of varieties of Cannabis

The Cannabis genus was first classified using the "modern" system of taxonomic nomenclature by Carolus Linnaeus in 1753, who devised the system still in use for the naming of species.[42] He considered the genus to be monotypic, having just a single species that he named Cannabis sativa L. (L. stands for Linnaeus, and indicates the authority who first named the species). Linnaeus was familiar with European hemp, which was widely cultivated at the time. In 1785, noted evolutionary biologist Jean-Baptiste de Lamarck published a description of a second species of Cannabis, which he named Cannabis indica Lam.[43] Lamarck based his description of the newly named species on plant specimens collected in India. He described C. indica as having poorer fiber quality than C. sativa, but greater utility as an inebriant. Additional Cannabis species were proposed in the 19th century, including strains from China and Vietnam (Indo-China) assigned the names Cannabis chinensis Delile, and Cannabis gigantea Delile ex Vilmorin.[44] However, many taxonomists found these putative species difficult to distinguish. In the early 20th century, the single-species concept was still widely accepted, except in the Soviet Union where Cannabis continued to be the subject of active taxonomic study. The name Cannabis indica was listed in various Pharmacopoeias, and was widely used to designate Cannabis suitable for the manufacture of medicinal preparations.[45]

20th century

In 1924, Russian botanist D.E. Janichevsky concluded that ruderalCannabis in central Russia is either a variety of C. sativa or a separate species, and proposed C. sativa L. var. ruderalis Janisch. and Cannabis ruderalis Janisch. as alternative names.[22] In 1929, renowned plant explorer Nikolai Vavilov assigned wild or feral populations of Cannabis in Afghanistan to C. indica Lam. var. kafiristanica Vav., and ruderal populations in Europe to C. sativa L. var. spontanea Vav.[28][44] In 1940, Russian botanists Serebriakova and Sizov proposed a complex classification in which they also recognized C. sativa and C. indica as separate species. Within C. sativa they recognized two subspecies: C. sativa L. subsp. culta Serebr. (consisting of cultivated plants), and C. sativa L. subsp. spontanea (Vav.) Serebr. (consisting of wild or feral plants). Serebriakova and Sizov split the two C. sativa subspecies into 13 varieties, including four distinct groups within subspecies culta. However, they did not divide C. indica into subspecies or varieties.[22][46] This excessive splitting of C. sativa proved too unwieldy, and never gained many adherents.

In the 1970s, the taxonomic classification of Cannabis took on added significance in North America. Laws prohibiting Cannabis in the United States and Canada specifically named products of C. sativa as prohibited materials. Enterprising attorneys for the defense in a few drug busts argued that the seized Cannabis material may not have been C. sativa, and was therefore not prohibited by law. Attorneys on both sides recruited botanists to provide expert testimony. Among those testifying for the prosecution was Dr. Ernest Small, while Dr. Richard E. Schultes and others testified for the defense. The botanists engaged in heated debate (outside of court), and both camps impugned the other's integrity.[32][33] The defense attorneys were not often successful in winning their case, because the intent of the law was clear.[47]

In 1976, Canadian botanist Ernest Small[48] and American taxonomist Arthur Cronquist published a taxonomic revision that recognizes a single species of Cannabis with two subspecies: C. sativa L. subsp. sativa, and C. sativa L. subsp. indica (Lam.) Small & Cronq.[44] The authors hypothesized that the two subspecies diverged primarily as a result of human selection; C. sativa subsp. sativa was presumably selected for traits that enhance fiber or seed production, whereas C. sativa subsp. indica was primarily selected for drug production. Within these two subspecies, Small and Cronquist described C. sativa L. subsp. sativa var. spontanea Vav. as a wild or escaped variety of low-intoxicant Cannabis, and C. sativa subsp. indica var. kafiristanica (Vav.) Small & Cronq. as a wild or escaped variety of the high-intoxicant type. This classification was based on several factors including interfertility, chromosome uniformity, chemotype, and numerical analysis of phenotypic characters.[26][44][49]

Professors William Emboden, Loran Anderson, and Harvard botanist Richard E. Schultes and coworkers also conducted taxonomic studies of Cannabis in the 1970s, and concluded that stable morphological differences exist that support recognition of at least three species, C. sativa, C. indica, and C. ruderalis.[50][51][52][53] For Schultes, this was a reversal of his previous interpretation that Cannabis is monotypic, with only a single species.[54] According to Schultes' and Anderson's descriptions, C. sativa is tall and laxly branched with relatively narrow leaflets, C. indica is shorter, conical in shape, and has relatively wide leaflets, and C. ruderalis is short, branchless, and grows wild in central Asia. This taxonomic interpretation was embraced by Cannabis aficionados who commonly distinguish narrow-leafed "sativa" drug strains from wide-leafed "indica" drug strains.[55]

Continuing research

Molecular analytical techniques developed in the late 20th century are being applied to questions of taxonomic classification. This has resulted in many reclassifications based on evolutionary systematics. Several studies of Random Amplified Polymorphic DNA (RAPD) and other types of genetic markers have been conducted on drug and fiber strains of Cannabis, primarily for plant breeding and forensic purposes.[56][57][58][59][60] Dutch Cannabis researcher E.P.M. de Meijer and coworkers described some of their RAPD studies as showing an "extremely high" degree of genetic polymorphism between and within populations, suggesting a high degree of potential variation for selection, even in heavily selected hemp cultivars.[27] They also commented that these analyses confirm the continuity of the Cannabisgene pool throughout the studied accessions, and provide further confirmation that the genus comprises a single species, although theirs was not a systematic study per se.

Karl W. Hillig, a graduate student in the laboratory of long-time Cannabis researcher Paul G. Mahlberg[61] at Indiana University, conducted a systematic investigation of genetic, morphological, and chemotaxonomic variation among 157 Cannabis accessions of known geographic origin, including fiber, drug, and feral populations. In 2004, Hillig and Mahlberg published a chemotaxomic analysis of cannabinoid variation in their Cannabisgermplasm collection. They used gas chromatography to determine cannabinoid content and to infer allele frequencies of the gene that controls CBD and THC production within the studied populations, and concluded that the patterns of cannabinoid variation support recognition of C. sativa and C. indica as separate species, but not C. ruderalis.[28] The authors assigned fiber/seed landraces and feral populations from Europe, central Asia, and Asia Minor to C. sativa. Narrow-leaflet and wide-leaflet drug accessions, southern and eastern Asian hemp accessions, and feral Himalayan populations were assigned to C. indica. In 2005, Hillig published a genetic analysis of the same set of accessions (this paper was the first in the series, but was delayed in publication), and proposed a three-species classification, recognizing C. sativa, C. indica, and (tentatively) C. ruderalis.[31] In his doctoral dissertation published the same year, Hillig stated that principal components analysis of phenotypic (morphological) traits failed to differentiate the putative species, but that canonical variates analysis resulted in a high degree of discrimination of the putative species and infraspecific taxa.[62] Another paper in the series on chemotaxonomic variation in the terpenoid content of the essential oil of Cannabis revealed that several wide-leaflet drug strains in the collection had relatively high levels of certain sesquiterpene alcohols, including guaiol and isomers of eudesmol, that set them apart from the other putative taxa.[63] Hillig concluded that the patterns of genetic, morphological, and chemotaxonomic variation support recognition of C. sativa and C. indica as separate species. He also concluded there is little support to treat C. ruderalis as a separate species from C. sativa at this time, but more research on wild and weedy populations is needed because they were underrepresented in their collection.

In September 2005, New Scientist reported that researchers at the Canberra Institute of Technology had identified a new type of Cannabis based on analysis of mitochondrial and chloroplast DNA.[64] The New Scientist story, which was picked up by many news agencies and web sites, indicated that the research was to be published in the journal Forensic Science International.[65]

Popular usage

The scientific debate regarding taxonomy has had little effect on the terminology in widespread use among cultivators and users of drug-type Cannabis. Cannabis aficionados recognize three distinct types based on such factors as morphology, native range, aroma, and subjective psychoactive characteristics. Sativa is the most widespread variety, which is usually tall, laxly branched, and found in warm lowland regions. Indica designates shorter, bushier plants adapted to cooler climates and highland environments. Ruderalis is the informal name for the short plants that grow wild in Europe and central Asia.

Breeders, seed companies, and cultivators of drug type Cannabis often describe the ancestry or gross phenotypic characteristics of cultivars by categorizing them as "pure indica," "mostly indica," "indica/sativa," "mostly sativa", or "pure sativa."

Uses

Cannabis is used for a wide variety of purposes.

Recreational use

Comparison of physical harm and dependence regarding various drugs.[66]

Cannabis is a popular recreational drug around the world, only behind alcohol, caffeine and tobacco. In the United States alone, it is believed that over 100 million Americans have tried cannabis, with 25 million Americans having used it within the past year.[67]

The psychoactive effects of Cannabis are known to have a biphasic nature. Primary psychoactive effects include a state of relaxation, and to a lesser degree, euphoria from its main psychoactive compound, tetrahydrocannabinol. Secondary psychoactive effects, such as a facility for philosophical thinking, introspection and metacognition have been reported amongst cases of anxiety and paranoia.[68] Finally, the tertiary psychoactive effects of the drug cannabis, can include an increase in heart rate and hunger, believed to be caused by 11-OH-THC, a psychoactive metabolite of THC produced in the liver.

Normal cognition is restored after approximately three hours for larger doses via a smoking pipe, bong or vaporizer.[68] However, if a large amount is taken orally the effects may last much longer. After 24 hours to a few days, minuscule psychoactive effects may be felt, depending on dosage, frequency and tolerance to the drug.

Cannabidiol (CBD), which has no psychotropic effects by itself[25] (although sometimes showing a small stimulant effect, similar to caffeine),[69] attenuates, or reduces[70] the higher anxiety levels caused by THC alone.[71]

According to Delphic analysis by British researchers in 2007, cannabis has a lower risk factor for dependence compared to both nicotine and alcohol.[72] However, everyday use of Cannabis can in some cases be correlated with psychological withdrawal symptoms such as irritability and insomnia,[68] and evidence could suggest that if a user experiences stress, the likeliness of getting a panic attack increases because of an increase of THC metabolites.[73][74] However, cannabis withdrawal symptoms are typically mild and are never life-threatening.[75]

Short-term use increases both minor and major adverse effects.[77] Common side effects include dizziness, feeling tired, vomiting, and hallucinations.[77]Long-term effects of cannabis are not clear.[78] Concerns including memory and cognition problems, risk of addiction, schizophrenia in young people, and the risk of children taking it by accident.[76]

Hemp

The term hemp is used to name the durable soft fiber from the Cannabisplant stem (stalk). Cannabis sativa cultivars are used for fibers due to their long stems; Sativa varieties may grow more than six metres tall. However, hemp can refer to any industrial or foodstuff product that is not intended for use as a drug. Many countries regulate limits for psychoactive compound (THC) concentrations in products labeled as hemp.

Hemp is valuable in tens of thousands of commercial products, especially as fibre[80] ranging from paper, cordage, construction material and textiles in general, to clothing. Hemp is stronger and longer-lasting than cotton. It also is a useful source of foodstuffs (hemp milk, hemp seed, hemp oil) and biofuels. Hemp has been used by many civilizations, from China to Europe (and later North America) during the last 12,000 years.[80][81] In modern times novel applications and improvements have been explored with modest commercial success.[82][83]

Ancient and religious uses

The Cannabis plant has a history of medicinal use dating back thousands of years across many cultures.[84] The Yanghai Tombs, a vast ancient cemetery (54 000 m2) situated in the Turfan district of the Xinjiang Uyghur Autonomous Region of the People's Republic of China, have revealed the 2700-year-old grave of a shaman. He is thought to have belonged to the Jushi culture recorded in the area centuries later in the Hanshu, Chap 96B.[85] Near the head and foot of the shaman was a large leather basket and wooden bowl filled with 789g of cannabis, superbly preserved by climatic and burial conditions. An international team demonstrated that this material contained tetrahydrocannabinol, the psychoactive component of cannabis. The cannabis was presumably employed by this culture as a medicinal or psychoactive agent, or an aid to divination. This is the oldest documentation of cannabis as a pharmacologically active agent.[86]

"While we have no evidence of the use of ephedra among the steppe tribes, we have already seen that they did share in the cultic use of hemp, a practice that ranged from Romania east to the Yenisei River from at least the 3rd millennium BC onwards where its use was later encountered in the apparatus for smoking hemp found at Pazyryk."[88]

Cannabis is first referred to in HinduVedas between 2000 and 1400 BCE, in the Atharvaveda. By the 10th century CE, it has been suggested that it was referred to by some in India as "food of the gods".[89] Cannabis use eventually became a ritual part of the Hindu festival of Holi.

In Buddhism, cannabis is generally regarded as an intoxicant and may be a hindrance to development of meditation and clear awareness. In ancient Germanic culture, Cannabis was associated with the Norse love goddess, Freya.[90][91] An anointing oil mentioned in Exodus is, by some translators, said to contain Cannabis.[92]Sufis have used Cannabis in a spiritual context since the 13th century CE.[93]

Reproduction

Breeding systems

Cannabis sativa fruits (achenes) that contain the seeds

Cannabis is predominantly dioecious,[14][101] although many monoecious varieties have been described.[102] Subdioecy (the occurrence of monoecious individuals and dioecious individuals within the same population) is widespread.[103][104][105] Many populations have been described as sexually labile.[58][106][107]

As a result of intensive selection in cultivation, Cannabis exhibits many sexual phenotypes that can be described in terms of the ratio of female to male flowers occurring in the individual, or typical in the cultivar.[108] Dioecious varieties are preferred for drug production, where typically the female flowers are used. Dioecious varieties are also preferred for textile fiber production, whereas monoecious varieties are preferred for pulp and paper production. It has been suggested that the presence of monoecy can be used to differentiate licit crops of monoecious hemp from illicit drug crops.[103] However, sativa strains often produce monoecious individuals, probably as a result of inbreeding.

Sex determination

Cannabis has been described as having one of the most complicated mechanisms of sex determination among the dioecious plants.[108] Many models have been proposed to explain sex determination in Cannabis.

Based on studies of sex reversal in hemp, it was first reported by K. Hirata in 1924 that an XY sex-determination system is present.[106] At the time, the XY system was the only known system of sex determination. The X:A system was first described in Drosophila spp in 1925.[109] Soon thereafter, Schaffner disputed Hirata's interpretation,[110] and published results from his own studies of sex reversal in hemp, concluding that an X:A system was in use and that furthermore sex was strongly influenced by environmental conditions.[107]

Since then, many different types of sex determination systems have been discovered, particularly in plants.[101] Dioecy is relatively uncommon in the plant kingdom, and a very low percentage of dioecious plant species have been determined to use the XY system. In most cases where the XY system is found it is believed to have evolved recently and independently.[111]

Since the 1920s, a number of sex determination models have been proposed for Cannabis. Ainsworth describes sex determination in the genus as using "an X/autosome dosage type".[101]

The question of whether heteromorphic sex chromosomes are indeed present is most conveniently answered if such chromosomes were clearly visible in a karyotype. Cannabis was one of the first plant species to be karyotyped; however, this was in a period when karyotype preparation was primitive by modern standards (see History of Cytogenetics). Heteromorphic sex chromosomes were reported to occur in staminate individuals of dioecious "Kentucky" hemp, but were not found in pistillate individuals of the same variety. Dioecious "Kentucky" hemp was assumed to use an XY mechanism. Heterosomes were not observed in analyzed individuals of monoecious "Kentucky" hemp, nor in an unidentified German cultivar. These varieties were assumed to have sex chromosome composition XX.[112] According to other researchers, no modern karyotype of Cannabis had been published as of 1996.[113] Proponents of the XY system state that Y chromosome is slightly larger than the X, but difficult to differentiate cytologically.[114]

More recently, Sakamoto and various co-authors[115][116] have used RAPD to isolate several genetic marker sequences that they name Male-Associated DNA in Cannabis (MADC), and which they interpret as indirect evidence of a male chromosome. Several other research groups have reported identification of male-associated markers using RAPD and AFLP.[27][58][117] Ainsworth commented on these findings, stating,

"It is not surprising that male-associated markers are relatively abundant. In dioecious plants where sex chromosomes have not been identified, markers for maleness indicate either the presence of sex chromosomes which have not been distinguished by cytological methods or that the marker is tightly linked to a gene involved in sex determination.[101] "

Environmental sex determination is known to occur in a variety of species.[118] Many researchers have suggested that sex in Cannabis is determined or strongly influenced by environmental factors.[107] Ainsworth reviews that treatment with auxin and ethylene have feminizing effects, and that treatment with cytokinins and gibberellins have masculinizing effects.[101] It has been reported that sex can be reversed in Cannabis using chemical treatment.[119] A PCR-based method for the detection of female-associated DNA polymorphisms by genotyping has been developed.[120]